Androgen receptor driven transcription in molecular apocrine breast cancer is mediated by FoxA1

Breast cancer is a heterogeneous disease and several distinct subtypes exist based on differential gene expression patterns. Molecular apocrine tumours were recently identified as an additional subgroup, characterised as oestrogen receptor negative and androgen receptor positive (ER- AR+), but with an expression profile resembling ER+ luminal breast cancer. One possible explanation for the apparent incongruity is that ER gene expression programmes could be recapitulated by AR. Using a cell line model of ER- AR+ molecular apocrine tumours (termed MDA-MB-453 cells), we map global AR binding events and find a binding profile that is similar to ER binding in breast cancer cells. We find that AR binding is a near-perfect subset of FoxA1 binding regions, a level of concordance never previously seen with a nuclear receptor. AR functionality is dependent on FoxA1, since silencing of FoxA1 inhibits AR binding, expression of the majority of the molecular apocrine gene signature and growth cell growth. These findings show that AR binds and regulates ER cis-regulatory elements in molecular apocrine tumours, resulting in a transcriptional programme reminiscent of ER-mediated transcription in luminal breast cancers.

Liquids with permanent porosity

Porous solids such as zeolites and metal-organic frameworks are useful in molecular separation and in catalysis, but their solid nature can impose limitations. For example, liquid solvents, rather than porous solids, are the most mature technology for post-combustion capture of carbon dioxide because liquid circulation systems are more easily retrofitted to existing plants. Solid porous adsorbents offer major benefits, such as lower energy penalties in adsorption-desorption cycles, but they are difficult to implement in conventional flow processes. Materials that combine the properties of fluidity and permanent porosity could therefore offer technological advantages, but permanent porosity is not associated with conventional liquids. Here we report free-flowing liquids whose bulk properties are determined by their permanent porosity. To achieve this, we designed cage molecules that provide a well-defined pore space and that are highly soluble in solvents whose molecules are too large to enter the pores. The concentration of unoccupied cages can thus be around 500 times greater than in other molecular solutions that contain cavities, resulting in a marked change in bulk properties, such as an eightfold increase in the solubility of methane gas. Our results provide the basis for development of a new class of functional porous materials for chemical processes, and we present a one-step, multigram scale-up route for highly soluble 'scrambled' porous cages prepared from a mixture of commercially available reagents. The unifying design principle for these materials is the avoidance of functional groups that can penetrate into the molecular cage cavities.

Investigating clinical predictors of arteriovenous fistula functional patency in a European cohort

Background: Arteriovenous fistula (AVF) failure to mature (FTM) rates contribute to excessive dependence on central venous catheters for haemodialysis. Choosing the most appropriate vascular access site for an individual patient is guided largely by their age, co-morbidities and clinical examination. We investigated the clinical predictors of AVF FTM in a European cohort of patients and applied an existing clinical risk prediction model for AVF FTM to this population.
Methods: A prospective cohort study was designed that included all patients undergoing AVF creation between January 2009 and December 2014 in a single centre (Belfast City Hospital) who had a functional AVF outcome observed by March 2015.
Results: A total of 525 patients had a functional AVF outcome recorded and were included in the FTM analysis. In this cohort, 309 (59%) patients achieved functional AVF patency and 216 (41%) patients had FTM. Female gender [P < 0.001, odds ratio (OR) 2.03 (CI 1.37–3.02)] and lower-arm AVF [P < 0.001, OR 4.07 (CI 2.77–5.92)] were associated with AVF FTM. The Lok model did not predict FTM outcomes based on the associated risk stratification in our population.
Conclusions: In this European study, female gender was associated with twice the risk of AVF FTM and a lower-arm AVF with four times the risk of FTM. The FTM risk prediction model was not found to be discriminative in this population. Clinical risk factors for AVF FTM vary between populations;we would recommend that units investigate their own clinical predictors of FTM to maximize AVF functional patency and ultimately survival in dialysis patients. Clinical predictors of AVF FTM may not be sufficient on their own to improve vascular access functional patency rates.

MHD Wave Modes Resolved in Fine-Scale Chromospheric Magnetic Structures

Due to its complex and dynamic fine-scale structure, the chromosphere is a particularly challenging region of the Sun's atmosphere to understand. It is now widely accepted that to model chromospheric dynamics, even on a magnetohydrodynamic (MHD) scale, while also calculating spectral line emission, one must realistically include the effects of partial ionization and radiative transfer in a multi-fluid plasma under non-LTE conditions. Accurate quantification of MHD wave energetics must befounded on a precise identification of the actual wave mode being observed. This chapter focuses on MHD kink-mode identification, MHD sausage mode identification, and MHD torsional Alfvén wave identification. It then reviews progress in determining more accurate energy flux estimations of specific MHD wave modes observed in the chromosphere. The chapter finally examines how the discovery of these MHD wave modes has helped us advance the field of chromosphericmagnetoseismology.

Ultra-High-Resolution Observations of MHD Waves in Photospheric Magnetic Structures

This chapter reviews the recent observations of waves and oscillations manifesting in fine-scale magnetic structures in the solar photosphere, which are often interpreted as the "building blocks' of the magnetic Sun. The authors found, through phase relationships between the various waveforms, that small-scale magnetic bright points (MBPs) in the photosphere demonstrated signatures of specific magnetoacoustic waves, in particular the sausage and kink modes. Modern magnetohydrodynamic (MHD) simulations of the lower solar atmosphere clearly show how torsional motions can easily be induced in magnetic elements in the photosphere through the processes of vortical motions and/or buffeting by neighboring granules. The authors detected significant power associated with high-frequency horizontal motions, and suggested that these cases may be especially important in the creation of a turbulent environment that efficiently promotes Alfvén wave dissipation.

O convento de Nossa Senhora da Assunção: (des)construção da memória

Dissertação mest., História da Arte Portuguesa, Universidade do Algarve, 2007

Global geriatric evaluation of the Algarve population

The ageing of population challenges communities to adapt and evolve to accommodate the needs of people that live longer (mostly out of work, either healthy, fragile or with chronic disease). Population ageing in the Algarve is higher than in overall Portugal. Studies on health conditions, frailty risk factors and elderly specific needs are undeveloped in Portugal and unknown in the Algarve. Objective To prepare a tool for Global Geriatric Evaluation, to be used in the “Survey of Health and Ageing in the Region of Algarve - SHARA”, a commitment to “European Innovation Partnership on Active and Healthy Ageing”. Methods A preliminary version of the screening tool, which includes well-known instruments to measure health condition (EASY-care), risk of fall (Tinetty), physical activity (Baecke’s modified questionnaire), nutritional condition (MNA), cognitive and depressive status (MMSE, Yesavage geriatric depression scale), together with socio-demographic characteristics, was applied to an independent sample of subjects from an elderly community centre - ARPI (“Associação de Reformados, Pensionistas e Idosos do Concelho de Faro”), with ages between 55 and 89. Results ARPI is mostly frequented by women, who either have risk of malnutrition or malnutrition incidence, a relevant risk of fall or are physically active. Those who live alone, show a higher risk of fall. Conclusions ARPI members are active, but with risk of malnutrition and fall, suggesting the relevance and importance of future interventions in these areas. The proposed screening tool showed to be adequate for the SHARA study, suitable to provide wider information on frailty.

A gestão de Stresse e estratégias de Coping em comerciais dos setores bancário e alimentar

Dissertação de mestrado, Gestão de Recursos Humanos, Escola Superior de Gestão, Hotelaria e Turismo, Universidade do Algarve, 2014

Spatial justice: law and the geography of withdrawal

While spatial justice could be the most radical offspring of law’s recent spatial turn, it remains instead a geographically informed version of social justice. The majority of the existing literature on the subject has made some politically facile assumptions about space, justice and law, thereby subsuming the potentially radical into the banal. In this article, I suggest that the concept of spatial justice is the most promising platform on which to redefine, not only the connection between law and geography, but more importantly, the conceptual foundations of both law and space. More concretely, the article attempts two things: first, a radical understanding of legal spatiality. Space is not just another parameter for law, a background against which law takes place, or a process that the law needs to take into consideration. Space is intertwined with normative production in ways that law often fails to acknowledge, and part of this article is a re-articulation of the connection. Second, to suggest a conception of spatial justice that derives from a spatial law. Such a conception cannot rely on given concepts of distributive or social justice. Instead, the concept of spatial justice put forth here is informed by post-structural, feminist, post-ecological and other radical understandings of emplacement and justice, as well as arguably the most spatial of philosophical discourses, that of Deleuze–Guattari and the prescribed possibilities of space as manifold.

Evaluation and Potential Cost-Effectiveness of Active Surveillance Pharmacovigilance for First-Line HAART in Namibia

Thesis (Ph.D.)--University of Washington, 2016-02

O papel da curadoria como difusora da arte contemporânea

Dissertação de Mestrado em Património, Museologia e Desenvolvimento

Use of Distress and Depression Thermometers to Measure Psychosocial Morbidity Among Southern European Cancer Patients

GOALS OF WORK: Recent literature has indicated the need for rapid evaluation of psychosocial issues secondary to cancer. Because of the problems of routine use of psychometric instruments, short instruments such as visual analogue scales or one-item 0-10 scales have been developed as valid assessment alternatives. PATIENTS AND METHODS: A study was conducted to examine the role of two 0-10 scales in measuring emotional stress (distress thermometer, DT) and depressed mood (mood thermometer, MT), respectively, in a multicenter study carried out in southern European countries (Italy, Portugal, Spain, and Switzerland). A convenience sample of 312 cancer outpatients completed the DT and MT and the Hospital Anxiety Depression Scale (HADS). MAIN RESULTS: DT was more significantly associated HADS anxiety than HADS depression while MT was related both to HADS anxiety and depression. The correlation of MT with HADS was higher than DT. A cutoff point >4 on the DT maximized sensitivity (65%) and specificity (79%) for general psychosocial morbidity while a cutoff >5 identified more severe "caseness" (sensitivity=70%; specificity=73%). On the MT, sensitivity and specificity for general psychosocial morbidity were 85% and 72% by using the cutoff score >3. A score >4 on the MT was associated with a sensitivity of 78% and a specificity of 77% in detecting more severe caseness. CONCLUSIONS: Two simple instruments, the DT and the MT, were found to have acceptable levels of sensitivity and specificity in detecting psychosocial morbidity. Compared to the HADS, however, the mood MT performed better than the DT.

Heparinized nanohydroxyapatite/collagen granules for controlled release of vancomycin

The purpose of this study was to develop a bone substitute material capable of preventing or treating osteomyelitis through a sustainable release of vancomycin and simultaneously inducing bone regeneration. Porous heparinized nanohydroxyapatite (nanoHA)/collagen granules were characterized using scanning electron microscopy, micro-computed tomography and attenuated total reflectance Fourier transform infrared spectroscopy. After vancomycin adsorption onto the granules, its releasing profile was studied by UV molecular absorption spectroscopy. The heparinized granules presented a more sustainable release over time, in comparison with nonheparinized nanoHA and nanoHA/collagen granules. Vancomycin was released for 360 h and proved to be bioactive until 216 h. Staphylococcus aureus adhesion was higher on granules containing collagen, guiding the bacteria to the material with antibiotic, improving their eradication. Moreover, cytotoxicity of the released vancomycin was assessed using osteoblast cultures, and after 14 days of culture in the presence of vancomycin, cells were able to remain viable, increasing their metabolic activity and colonizing the granules, as observed by scanning electron microscopy and confocal laser scanning microscopy. These findings suggest that heparinized nanoHA/collagen granules are a promising material to improve the treatment of osteomyelitis, as they are capable of releasing vancomycin, eliminating the bacteria, and presented morphological and chemical characteristics to induce bone regeneration.